Protein tyrosine phosphatases (PTPs) are an enzyme family comprising multiple enzyme subtypes, or isozymes, with differential activity and various distributions in the body. PTPs control a broad spectrum of cellular processes, for example, proliferation, differentiation, migration, apoptosis, and the immune responses (Alonso et al., 2004; Tonks, 2006). Dysfunction of PTP activity is associated with cancers, metabolic syndromes, and autoimmune disorders (Zhang, 2001). Compounds that can selectively inhibit particular PTPs are useful tools for studying the role of specific PTPs in normal and disease processes. Therapeutic compounds that can selectively inhibit specific PTPs are advantageous for treating diseases associated with excessive activity of a particular PTP. Use of a selective PTP can reduce the potential for undesirable effects due to nonselective inhibition of PTPs. However, the development of selective PTP inhibitors is problematic, in part due to the common architecture of the active site (i.e. pTyr-binding pocket) shared by members of the PTP family. Given the importance that these enzymes play in human and animal health there is currently a profound need for molecules that can preferentially inhibit some of these enzymes. Various aspects of the present invention address this need.